The present proposal is the result of the interaction of geneticists, embryologists, molecular biologists, cell biologists, immunologists and virologists of the Wistar Institute in studies of the relationship between cell differentiation and cancer and of the regulation of gene expression in stem versus differentiated cells. A variety of experimental approaches and cellular systems will be used by the different investigators to probe erythroid, myeloid and lymphoid differentiation and to understand their relation to cancers of the hematopoietic system. Mouse embryonic and teratocarcinoma cells will be used to determine what factors affect the transition from the normal embryonic to embryonal carcinoma (EC) cells and to determine whether the malignant behavior of EC cells is the result of epigenetic changes. The mechanisms of control of gene expression in pluripotent and totipotent mouse and human teratocarcinoma-derived stem cells will be investigated with DNA and RNA tumor viruses as probes. The use of monoclonal antibodies produced by hybridomas to study surface antigens expressed at different stages of cell differentiation will be stressed.